(a) Field of the Invention
This invention relates to novel derivatives of 4,5-dihydro-4-oxofuran-2-carboxylic acid, to therepeutically acceptable salts thereof, to processes for their preparation, to methods for using the derivatives and to pharmaceutical compositions of the derivatives.
More specifically, the present invention relates to novel derivatives of 4,5-dihydro-4-oxofuran-2-carboxylic acid having two substituents at position 5 and in addition being optionally further substituted at position 3 with a lower alkyl group as well as esters thereof. These derivatives are useful as hypolipidemic agents in a mammal at dosages which do not elicit undesirable side effects.
(b) Description of the Prior Art
4,5-Dihydro-4-oxofuran derivatives are extensively described in the literature. Additionally, derivatives of 4,5-dihydro-4-oxofuran-carboxylic acids have also been disclosed. For example, 4,5-dihydro-2-methyl-4-oxofuran-3-carboxylic acid and its ethyl ester are described by R. E. Rosenkranz et al., Helv. Chim. Acta. 46,1259(1963) and references cited therein. In addition, this reference discloses the structure of 4,5-dihydro-5-methyl-4-oxofuran-2-carboxylic acid as a hypothetical intermediate during the decarboxylation of 4-methoxy-5-methylfuran-2-carboxylic acid. The presence of 4,5-dihydro-5-methyl-4-oxofuran-2-carboxylic acid was not confirmed by isolation or other means.
Recently a few furan derivatives were reported to be hypolipidemic agents. More specifically, some derivatives of 2,3,4,5-tetrahydro-3-oxo-4-hydroxy-iminofurans, 2,5-dihydrofurans and 2,3,4,5-tetrahydrofurans are described to have weak to moderate hypolipidemic activity by G. B. Bennett et al., J. Med. Chem., 19,709 (1976). However, the latter report also states that the furan derivatives, disclosed therein, are devoid of a desirable level of hypolipidemic activity.
The 4,5-dihydro-4-oxofuran-2-carboxylic acid derivatives of this invention are novel compounds having hypolipidemic activity without affecting liver weight.